Survival of patients after lung transplantation is significantly lower compared to other solid organ transplants, which may be attributed to the unique physiological characteristics of the lungs and difficult dosing of immunosuppressive drugs due to their high pharmacokinetic variability.
The aim of this master's thesis was to evaluate how well the existing literature population pharmacokinetic models for tacrolimus after lung transplantation describe the measured tacrolimus concentrations in the study population. We also investigated the effects of biochemical, genetic and clinical factors on the variability of tacrolimus pharmacokinetics, determined their statistical significance, and developed a final population pharmacokinetic model that included significant covariates.
The final model is a two-compartment model with the following parameter values and their IIVs: ktr = 6.97 h–1 (41.1%), CL/F = 11.4 L/h (35.6%), V1/F = 126 L (46.4%), V2/F = 569 L (200%), Q/F = 41.2 L/h (70.0 %), including the effects of the following covariates on the clearance: time after transplantation (TAT), haematocrit, serum creatinine concentration, serum protein concentration, concurrent treatment with posaconazole, voriconazole, metronidazole, or fluconazole, concurrent treatment with clarithromycin, and concurrent treatment with testosterone.
The population pharmacokinetic model developed may help optimise the tacrolimus dosing regimen after lung transplantation.
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